Adolor Corp. unveiled positive Phase III data on Entereg (alvimopan), its partnered product for postoperative ileus, boosting shares in the company.
David Madden, Adolor’s interim president and CEO, said in a conference call that the news "represents a significant milestone" for the Exton, Pa.-based company and its lead product. He added that the top-line results "provide the basis for a compelling response" to an FDA approvable letter received last summer requiring additional proof of efficacy, and Adolor intends to submit by June final results from the trial, called Study 314, as part of its complete response. That, Madden said, "should trigger a six-month review clock."
The Street responded favorably to the news that Adolor likely would avoid another trial, and reduced risk for the narcotic bowel dysfunction trial, also called opioid-induced constipation. The company’s stock (NASDAQ:ADLR) jumped 41.4 percent Wednesday, or $6.53, to close at $22.29. Analyst Greg Wade said the product should receive FDA approval in the time frame laid out by the company and predicted the FDA could convene an advisory panel hearing on the product in the fourth quarter, although Madden said such a meeting could not yet be forecast.
"Clearly the data suggest that the company has an opportunity now to get the drug approved in the postoperative ileus setting," Wade told BioWorld Today, adding that it was more important to succeed in Study 314, a trial "people had perceived to be risky."
"There’s a great deal of enthusiasm toward the company for the next indication," he said.
Wade, who works for Pacific Growth Equities in San Francisco, said partner GlaxoSmithKline plc is expected to release Phase III data in opioid-induced constipation in the second half of this year.
The latest postoperative ileus data showed that a 12-mg dose of the drug allowed bowel resection patients to return to normal gastrointestinal function (GI2) 20 hours sooner than placebo (p<0.001). The study’s primary endpoint, it is a composite measure of the time to recovery of both upper and lower gastrointestinal function, as defined by the time it takes for a patient to tolerate solid foods and have an initial bowel movement, whichever occurred last. Wade said the findings on that endpoint are "relatively aligned" with prior data on the same measure.
The initial dose was to be administered 30 to 90 minutes prior to surgery, a nearer point in time compared to previous Phase III studies, in which the first dose was required to be administered at least 120 minutes prior to surgery.
Entereg also achieved statistically significant differences compared to placebo for each of the secondary time-to-event endpoints, including another measure of time to recovery of gastrointestinal function (GI3) and time to discharge order written. For the former, Entereg patients recovered 16 hours sooner than those on placebo (p<0.001), and for the latter, they received discharge orders about 18 hours sooner than placebo patients (p<0.001).
Entereg, a peripherally acting mu-opioid receptor antagonist, is designed to inhibit the negative effects of opioids on the gastrointestinal system without interfering with the analgesic effects on the central nervous system. It was generally well tolerated in the trial, which randomized 654 patients into the study drug or placebo arms. The most frequently reported adverse events both in the alvimopan and placebo groups were nausea, vomiting and abdominal distention, and nausea and vomiting were reduced by statistically significant amounts.
Entereg’s new drug application for postoperative ileus was filed almost two years ago on efficacy data from three earlier Phase III studies. Later that year, the product failed to meet the primary endpoint in a Phase III study meant to support a European filing. (See BioWorld Today, May 10, 2004, and Dec. 27, 2004.)
The partners have a potential $270 million worldwide collaboration on Entereg for postoperative ileus and the gastrointestinal side effects of opioids, with the latter indication in a broad pivotal program that got under way last summer. It comprises three studies expected to enroll about 1,700 patients in North America, Europe and other parts of the world. (See BioWorld Today, Sept. 13, 2005.)
"Now that this risky event [Study 314] is out of the way," Wade said, "one can be involved in the stock and potentially realize some upside if the Phase III studies in the other indication turn out as one expects they will."
Terms of the relationship with London-based GlaxoSmithKline call for Adolor to pay all sales and marketing expenses for the first three years it is on the market in the U.S., in exchange for 45 percent of postoperative ileus revenues. After that, Adolor will receive half the profits in that setting with both companies supporting sales and marketing efforts. Outside the U.S., Adolor is to receive a royalty on sales. For the narcotic bowel dysfunction indication, Adolor is entitled to receive either 35 percent of profits or about 20 percent of top-line sales, should it elect to do so.
Wade estimated that Entereg could achieve $384 million in U.S. sales for postoperative ileus by 2011, and $695 million that year in the narcotic bowel dysfunction setting.
In addition to Entereg, Adolor has a sterile lidocaine patch in Phase II development for postsurgical incisional pain. The company’s earlier-stage discovery research programs are focused on identifying new compounds for pain.